It will be investigated which of the three antigens associated with rat colorectal carcinomas are most important inducing tumor isograft rejection in vivo, Special emphasis will be given to the embryonal antigens, both the tissue-type specific and the wide-spread antigen to augment their immunogenicity and modify the immune responses in vivo and in vitro to increased cell-mediated immunity and decreased blocking activity. Sequential studies on tumor immunity will be performed in rats with primary colon carcinomas and isografts of such neoplasms. The effects of immune manipulations involving treatment with cyclophosphamide and 5-FU combined with lymphocyte transfers, administration of "unblocking" antisera and inoculation of modified carcinoma cells with or without imunostimulators on tumor growth, as demonstrated by an established double contrast radiological technique, will be correlated with the effects on various immune parameters including tumor specific CMI, serum-blocking, and various other antibody activities. Similar studies will be performed on patients with colon carcinoma and undergoing surgery and chemotherapy and also on individuals with benign and premalignant bowel lesions. BIBLIOGRAPHIC REFERENCES: Steele, g., Jr., Sjogren, H.O., Rosengren, J.E., Lindstrom, C., Larsson, A., and Leandoer, L.: Sequential studies of serum blocking activity in rats bearing chemically induced primary bowel tumors. J. Natl. Cancer Inst., 54:959-967, 1975. Steele, G., Jr., Sjogren, H.O., and Price, M.R.: Tumor-associated and embryonic antigens in soluble fractions of a chemically induced rat colon carcinoma. Int. J. Cancer, 16: 33-51, 1975.